Use of n-acetyl-d-glucosamine in the manufacture of pharmaceutical useful for preventing and treating sexual disorder

ABSTRACT

The present invention has disclosed a use of N-acetyl-D-glucosamine in the preparation of a medicine for preventing and treating the sexual disfunction. The preparation taken N-acetyl-D-glucosamine as a main active component has been used to prevent and cure the sexual disfunction, and has the merits of remarkable curative effect, easy to prepare, no side effect and so on.

TECHNICAL FIELD

[0001] The present invention relates to the use ofN-acetyl-D-glucosamine and pharmaceutical acceptable salts thereof inthe manufacture of a medicament for preventing and treating the sexualdisfunction.

BACKGROUND ART

[0002] At present, there are many kinds of medicines for preventing andtreating the sexual disfunction in China and other countries, which aremainly divided into two big categories: (1) the medicines with viagra asa representative one, which acts on the endothelium cell of blood vesselfor regulating and improving the blood flux in the sexual organs andimproving the sexual disfunction one-pass in a short period. But thismedicine has a shortcoming of having a large side effect ofsubstantially influencing cardiac function; (2) Chinese traditionalmedicines, which are able to benefit liver and kidney by systematicregulation and has a certain effect, but their starting-effect is tooslow. So it is necessary to develop a new medicine for preventing andtreating the sexual disfunction.

[0003] In the research of “bio-waves” theory, the present inventor hasset up a bacterial wave growth model. Through researching, it is knownthat this wave is of its intrinsic regulation mechanism: some chemicalsubstances are able to participate the regulation in the bio-waveprocess, so as to transform an abnormal periodic slow wave into a normalphysiological chaotic quick wave, and this kind of substances are knownas promoting wave factors. Through separating, purifying andidentifying, it is determined that one of the factors isN-acetyl-D-glucosamine, the promoting wave function of which is shown inregulating the coupling oscillation of cellular membrane protein andsugar coating. Many biochemical and physiological process of human bodyneed the participation of the promoting wave factors, and it would leadto an abnormal state, if this kind of promoting wave factors is lackedin the living body.

[0004] N-acetyl-D-glucosamine is a chemical reagent. From the 1990's, itis continually used to treat pericementitis (WO9102530A1),microbiological infection (WO9718790A3), intestinal inflammation(WO9953929A1), cornea disease (JP10287570A2), hypertrophy of theprostate (U.S. Pat. No. 05,116,615) and so on. It is also applied incosmetology (JP59013708A2), shampoo preparation (JP2011505A2), tissuegrowth regulation agent (WO/A 8 702244), and etc., but it has not beenused in the manufacture of a medicament for preventing and treatingsexual disfunction.

[0005] The applicant of the present invention is surprised to find thatN-acetyl-D-glucosamine and pharmaceutical acceptable salts thereof areable to prevent and cure sexual disfunction quickly and efficiently, andsaid compounds almost have no toxicity. Therefore, this agent canovercome the shortcomings existed in the current medicaments forpreventing and treating sexual function as mentioned above.

CONTENTS OF THE INVENTION

[0006] Therefore, the present invention is related to the use ofN-acetyl-D-glucosamine and pharmaceutical acceptable salt thereof in themanufacture of a medicament for preventing and treating sexualdisfunction.

[0007] On the other hand, the present invention is related to a methodfor preventing and treating sexual disfunction, including administratingto a patient who is in need thereof an effective amount ofN-acetyl-D-glucosamine and pharmaceutical acceptable salts thereof toprevent and cure the sexual disfunction.

[0008] The molecular formula of N-acetyl-D-glucosamine is C₈H₁₅NO₆, itsstructure is as follows:

[0009] N-acetyl-D-glucosamine can be purchased in market or preparedaccording to a known method. For instance, patent application WO97/31121has disclosed a method for preparing N-acetyl-D-glucosamine from chitinby enzyme method, Japanese patent application JP63273493 has disclosed amethod in which chitin is partially hydrolyzed into N-acetyl-chitose,and then it is treated with enzyme to obtain N-acetyl-D-glucosamine.

[0010] The pharmaceutical acceptable salts of N-acetyl-D-glucosaminethat can be mentioned are the salts formed with pharmaceuticalacceptable acids, for instance, the salts formed with inorganic acids,such as hydrochloride, hydrobromide, borate, phosphate, sulfate sulfiteand hydrophosphate, and the salts formed with organic acids, such ascitrate, benzoate, ascorbate, methyl sulfate, naphthalene-2-sulfonate,picrate, fumarate, maleate, malonate, oxalate, succinate, acetate,tartrate, mesylate, tosylate, isethionate, α-ketoglutarate, α-glycerylphosphate and glucose-1-phosphate.

[0011] Generally, the compound of the present invention is administratedby oral, parenteral, sublingual, or penetrating skin, preferably,administrated by oral. In the course of treating sexual disfunctionaccording to the present invention, the amount of active component to betaken is dependent upon the features and seriousness of the disease andthe weight of the patient body. The preferred dosage unit usuallycomprises 5˜1000 mg, favorably 10˜700 mg, preferably 20˜500 mg product.Preferably, the concentration of the active component in the medicalpreparation is 0.1˜10% (by weight). These unit dosages are generallyadministrated once or more times daily and the total dosage for a personto be taken daily is varied in the range from 10 to 1000 mg, preferably50˜5000 mg/day, for instance, 100˜1000 mg/day, more often 100˜500mg/day.

[0012] The pharmaceutical composition of the invention for treating theindication mentioned above are suitable for administration by oral,sublingual, subcutaneous, intramuscle, intravein, penetrating skin, orrectum, the active component is able to be applied to animal and humanbeing in the form of dosage unit, such as in the form of freeze dryingproduct or be mixed form with conventional pharmaceutical carrier. Asuitable unit form of administration includes oral form, such as orallydispersible tablet, capsule, powder, granule and solution or suspension;the form for administrating via sublingle or buccal; the form foradministrating via subcutaneous, intramuscle or intravein; the form forlocal or rectum administration. The prepared preparation for oraladministration is particularly aqueous solution, alcoholic solution andcapsule.

[0013] Solid composition in the form of tablet are made by mixing themain active component with pharmaceutial excipient, such as gelatin,starch, lactose, magnesium stearate, talc powder, Arabic gum and etc.,The tablet is able to be coated with sugar or other suitable substances,or making them possess a persistent and delayed function and continuallyrelease pre-determined amount of active component.

[0014] The preparation in from of capsule can be obtained by mixingactive component with diluent, and filling the obtained mixture intosoft or hard capsule.

[0015] The preparation in the form of syrup or elixer may compriseactive component and sweetener that would better have no caloric, methylp-hydroxybenzoate and propyl p-hydroxybenzoate as antiseptic agent, andfragrancing agent and suitable coloring material.

[0016] The water-dispersible powder and granular preparation maycomprise active component, mixed with dispersing agent or wetting agent,or suspending agent, such as polyvinylpyrrolidone, and sweetener ortaste regulating agent.

[0017] The suppository for rectum administration is prepared with anadhesive which is melted at the same temperature as that of rectum, suchas cocoa oil or polyethylene glycol.

[0018] The injectable aseptic aqueous solution, salt solution, alcoholicsolution or homogenous suspension of the compound of the presentinvention can be administrated parenterally.

[0019] The applicant of the present invention believes that, throughregulating bio-waves, promoting redistribution of cell and couplingoscillation between sugar coatings of cell membrane acceptor andprotein, raising the sensitiveness of the local sexual hormone acceptorof sexual organ can quickly and effectively prevent and cure the sexualdisfunction and have a stable curative effect in a long period.

Optimal Mode for Carrying Out the Invention

[0020] The following experimental examples are used to illustrate thepromoting wave function, low toxicity and effectiveness for preventingand treating the sexual disfunction of the compound of the presentinvention (the compound of formula (I)).

[0021] I. Promoting wave test of the compound of formula (I)

[0022] 1. Experimental materials and method:

[0023] 1.1 Samples: pure compound of formula (I)

[0024] 1.2 Experimental materials:

[0025] Strain: Proteus Mirabilis (which should comply with the followingbiological reaction characteristics: dynamics (+), urease (+), lactose(−), glucose (+), H₂S (−), phenylalanine deaminase (+).

[0026] Culture medium: modified LB culture medium (the component of thecomposition are: trytones of 1%, yeast extract of 0.5%, sodium chloride1%, glucose of 0.1%, TTC of 0.002% and pH=7.2˜7.4).

[0027] 1.3 Experimental method:

[0028] The Proteus Mirabilis were inoculated at the center of LB plate,incubating at 37° C. for 9 hours, then there were concentric ringsemerged, which were extended outward continually with an interval of 3hours, and this was taken as a control; adding the compound of formula(I) with final concentration of 0.5% onto the LB plate, The ProteusMirabilis were innoculated by the same method, cultured at 37° C., andthe result showed that not only the concentric rings formed with aninterval of 3 hours were emerged, comparing with the control, it can beseen that there were also many fine waves on each ring emerged.

[0029] 2. Experimental results and evaluation:

[0030] The experiment adopts a bio-wave model which is used to researchthe promoting wave function of the compound of formula (I). It can beseen from the result that the compound of formula (I) was not only ableto cause bacterial cell to reveal a normal bio-wave characteristic, butalso cause the wave reveal finer wave mode so as to make the wave periodto be shorten, and these indicated that the compound of formula (I) havepromoting function to bio-waves, and the promoting wave function is ableto participate regulation of the re-distribution function of the cellsin the body and the two-step effect of conducting sexual excitation ledby sexual hormone acceptor on the membrane surface, so that this is abasis of the function for preventing and treating the sexual disfunctionof the compound of formula (I).

[0031] II. Toxicological test of the compound of formula (I), including:

[0032] 1. acute toxicity test: including tests of administratingmedicine by oral, intravenous injection and maximum limit amount foradministration;

[0033] 2. Ames test;

[0034] 3. micronucleus test of bone marrow cell of small mouse;

[0035] 4. abnormal sexual test for the sperm of mouse;

[0036] 5. abnormal aberrance test for the chromosin of mouse's testis;

[0037] 6. chronic lethal test;

[0038] 7. subchronic toxicity (feed for 90 days) test;

[0039] 8. traditional deformity-inducing test;

[0040] The results from these tests show that in the acute toxicity testof the compound of formula (I), the dosage more than 2 g/kg is taken,which is 300 times than the injection dosage for human being, but theacute toxicosis reaction had not appeared yet; in the long-periodtoxicity test, the maximum dosage has reached up to 1 g/kg, and afterthe treatment and observation for four weeks, there is no intoxicationreaction yet; and in the reproduction test, the mouse was feed fromroutine dosage of 7 mg/kg for 3 generations, it has been proved that thecompound of formula (I) has no influence on the pregnancy, birth, nurseand the growth of baby mouse, so it is proved that the compound offormula (I) is a substance without toxicity.

[0041] III. Clinic tests

[0042] 32 examples of male patients were picked out, who had beenrepeatedly treated for sexual disfunction with current treatment method,but these treatments were failed, the patients are classified clinicallyinto heavy, medium and light degree disease, separately administratedwith N-acetyl-D-glucosamine in the form of capsule by oral (500 mg/day)and alcoholic solution (50 mg/1000 ml) by oral (10 ml/day), using twoweeks as a period of treatment, and before and after the administration,and comparing the condition of the patient's symptom by detectingluteinizing hormone (LH), follicular stimulating hormone (FSH),prolactin (PRL), testosterone (T), estradiol (E2) and local blood flux.The results showed that, after treatment, 23 patients became normal,other 7 patient had been turned from heavy and medium degree into lightdegree of the clinic classification, 2 patients were failed (one of themwas more than 70 years old, and the another one was suffered fromprostate swelling, which influenced on the curative effect). The curerate is 72%, the total effective rate is 90 % (showed by certificationsof clinic treating effects). The time for administration coming intoeffect was from 1 hour after first administrating medicine to one weekafter continually administrating the medicine, so it is different intime. After treatment, the curative effect was steady and could bemaintained for a long time. In another test for volunteers, a voluntarypatient suffered from disfunction for more than ten years had taken byoral 12 grains of capsules (500 mg/grain) of the compound of formula (I)in three days, then his sexual function was recovered to normal, andkeep normal over two years up to now.

1. A use of N-acetyl-D-glucosamine and pharmaceutical acceptable saltsthereof in the manufacture of a medicament for preventing and treatingthe sexual disfunction.
 2. The use according to claim 1, wherein saidmedicament is in the form of oral preparation.
 3. The use according toclaim 2, wherein the form of the medicament is aqueous solution,alcoholic solution or capsule.
 4. The use according to any one of claims1˜3, wherein in said medicament, the concentration ofN-acetyl-D-glucosamine is 0.1˜10% by weight.
 5. The use according to anyone of claims 1˜3, wherein said medicament is for administration with adosage of 10˜1000 mg daily for each adult.
 8. (New) The method accordingto claim 7, wherein said medicament is in the form of aqueous solution,alcoholic solution or capsule.
 9. (New) The method according to claim 6,wherein the daily dosage for administration is in the range of 10˜1000mg of N-acetyl-D-glucosamine and/or pharmaceutically acceptable saltsthereof for each adult.
 10. (New) The method according to claim 7,wherein the daily dosage for administration is in the range of 10˜1000mg of N-acetyl-D-glucosamine and/or pharmaceutically acceptable saltsthereof for each adult.
 11. (New) The method according to claim 8,wherein the daily dosage for administration is in the range of 10˜1000mg of N-acetyl-D-glucosamine and/or pharmaceutically acceptable saltsthereof for each adult.